Acta Medica 2015; 4: 5–7
acta medica
TECHNICAL NOTE
Symptomatic hypocalcemia due to Shohl’s solution in a newborn
with galactosemia and a solitary kidney
H. Tolga ÇELIK1, [MD]
Elif TEKBAŞ2, [MD]
Şule YIĞIT3, [MD]
Murat YURDAKÖK3, [MD]
1 Hacettepe University Faculty of Medicine,
Department of Pediatrics, Division of
Neonatology
2 Hacettepe University Faculty of Medicine,
Department of Pediatrics
3 Hacettepe University Faculty of Medicine,
Department of Pediatrics, Division of
Neonatology
A BST R AC T
Proximal tubular defects (renal Fanconi syndrome) may occur secondary to
some inborn errors of metabolism. Shohl’s solution is used in renal Fanconi
syndrome for the treatment of metabolic acidosis. Herein, we report a newborn with galactosemia, a solitary kidney and renal Fanconi syndrome who
developed hypocalcemic convulsions under Shohl’s solution treatment.
Experience and knowledge regarding treatment with Shohl’s solution in neonates is limited. We thus recommend that clinicians should be cautious regarding the possibility of hypocalcemia while administering Shohl’s solution
in newborns.
Key words: Hypocalcemia, Shohl’s solution, newborn.
* Corresponding Author: H. Tolga Çelik
Hacettepe University Faculty of Medicine,
Department of Pediatrics, Division of
Neonatology,
Sihhiye, 06100 Ankara, Turkey
[email protected]
Received 7 December 2014; accepted 22 December 2014;
published online 13 January 2015
Introduction
Proximal tubular defects may occur secondary to
some inborn errors of metabolism, such as cystinosis, tyrosinemia type 1, galactosemia, oculocerebrorenal syndrome (Lowe’s syndrome), Wilson’s disease, and hereditary fructose intolerance. This condition is referred to as renal Fanconi syndrome and
is associated with impaired reabsorption of amino
acids, phosphate and glucose as well as bicarbonate. Administration of alkali treatment such as sodium bicarbonate, Shohl’s solution may be required to
normalize plasma HCO3–levels (1).
Herein, we report a newborn with galactosemia,
solitary kidney and renal Fanconi syndrome who
developed seizures due to hypocalcemia while under Shohl’s solution treatment.
Case presentation
A male infant from the first gestation of an 18 –yearold mother was delivered by cesarean section subsequent to a 39 weeks of gestation, weighing 3250 g.
There was no consanguinity between parents. The
© 2015 Acta Medica. All rights reserved.
baby was fed with breast-milk only. On the third day
of life, jaundice developed, and he received phototherapy until the seventh day of life. He was admitted to a local hospital for unresolved jaundice and
weight loss and during the subsequent evaluation
hepatomegaly and cholestasis were detected, as additional pathologies. At 17 days of age, he was referred to our hospital. On admission, his body weight
was 2810 g (3rd percentile), length 50 cm (10th percentile) and head circumference 35 cm (10–25th percentile). The physical examination revealed body weight
loss (440 g, 13.5 %), yellow-green discoloration of the
skin and hepatomegaly; other signs were normal.
Laboratory examination on admission revealed
cholestasis (total/direct bilirubin 7.7/6.24 mg/dl),
mild hypertransaminasemia (alanine/aspartate aminotransferase [ALT/AST] 49/127 mg/dl), and elevated alkaline phosphatase (813 IU/L). Serum biochemical analysis revealed sodium 145 mEq/L, potassium
3.7 mEq/L, chloride 116 mEq/L, urea 14.1 mg/dL,
creatinine 0.72 mg/dL, calcium 9.8 mg/dL, ionized
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Airway management with cervical spine injury
calcium 1.2 mg/dL, phosphorus 2.6 mg/dL, blood
glucose 56 mg/dL, and gamma glutamyl transpeptidase 25 mg/dL. Blood gas analysis was normal (pH7.33, PCO2 36.8 mmHg, HCO3 19.3 mEq/L).
Urine analysis revealed low pH (5.5), proteinuria
(300 mg/dL), generalized aminoaciduria, glucosuria
(200 mg/dL), and normal density. Urinary reducing substances were detected as positive (++++) and
wide galactose spot was shown by urine chromatography. A diagnosis of galactosemia was made, breastfeeding was stopped, and lactose-galactose-free formula was started. Shohl’s solution (140 g citric acid
and 98 g sodium citrate in 1000 mL distilled water) at a daily dose of 2 mEq/kg was initiated to prevent development of metabolic acidosis with a diagnosis of renal Fanconi syndrome. Abdominal-renal
ultrasonography demonstrated hepatomegaly, contracted gallbladder and enlarged right kidney (vertical length 64 mm), but the left kidney was not visualized. There was no bacterial growth on urine culture. After seven days (on the 28th day of life), the
patient developed a generalized seizure. We detected hypocalcemia (total calcium 6.49 mg/dL, ionized calcium 0.88 mEq/L, phosphorus 10.6 mg/dL)
as the underlying etiology leading to seizure; other
serum biochemical findings were normal. Plasma
parathormone level was 200 pg/mL (normal range
10-60 pg/mL), plasma magnesium 1.51 mg/dL (normal range 1.6-3 mg/dL), serum pH 7.37, plasma
HCO3 29.9 mmol/L. Urine pH 7.0 and density 1002,
and no proteinuria or glucosuria were detected concomitantly. Lumbar puncture was performed, showing normal protein and glucose levels (63.7 mg/dL,
46 mg/dL, respectively); no leukocytes or bacteria
were detected, and culture was negative. Dietary
daily intake of elementary calcium was 140 mg/kg
and of phosphorus was 68 mg/kg. Symptomatic hypocalcemia was treated with intravenous calcium
gluconate infusion (50 mEq/kg/day), and Shohl’s
solution was stopped and was not given again. No
seizures were observed after calcium infusion initiation. The calcium infusion treatment was stopped
by the 2ndday. The patient was discharged on the
30th day of life with normal blood calcium and phosphorus levels. Homozygous galactose-1-phosphate
uridyl transferase mutation was detected in genetic analysis.
When the patient was five-months-old 1.7 mCi
99m
TcDMSA scintigraphy was performed and left
renal agenesis was confirmed. It was detected by
scintigraphy that the right kidney was in normal
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dimension and location, with no cortical damage.
No uptake was observed at the left renal region and
at any ectopic location.
The last time the patient came to our outpatient
clinic for control was at 3.5 years of age. The blood
calcium, phosphorus, PTH, 25-OH vitamin D levels
and urinalyses performed during the outpatient follow-up has remained normal.
Discussion
Shohl’s solution is used in tubular function defects
such as distal renal tubular acidosis (dRTA) and renal Fanconi syndrome for the treatment of metabolic acidosis in pediatric patients (1,2). In this case,
we thought that renal Fanconi syndrome developed
secondary to galactosemia, and Shohl’s solution
was initiated to prevent the occurrence of metabolic acidosis.
As these diseases are not frequently observed in
the neonatal period, experience and knowledge regarding treatment with Shohl’s solution in neonates
is limited. In the literature, there are a few case reports about some adverse effects of Shohl’s solution
administration in children (3). Vomiting and diarrhea in a newborn with distal renal tubular acidosis during Shohl’s solution treatment has previously
been reported which was reversed by the cessation of
the Shohl’s solution (3). In our patient in the current
report, gastrointestinal symptoms were not observed.
Shohl’s solution includes citric acid and sodium
citrate. Profound hypocalcemia caused by parenteral
citrate was reported in an elderly adult patient with
multiple organ failure and rhabdomyolysis. This patient had received parenteral citrate treatment to
provide regional anticoagulation of the extracorporeal circuit. On follow–up, the patient had developed hypocalcemia requiring increasing amounts of
intravenous calcium replacement. The cause of hypocalcemia was related to the binding of citrate with
ionized calcium, in addition to sequestration of intracellular calcium due to the rhabdomyolysis in this
particular patient (4).
It is known that the ionized calcium level decreases in an alkaline environment. As the plasma
pH values were in normal ranges during the treatment with Shohl’s solution in this case, we attributed the symptomatic hypocalcemia to binding of citrate to calcium.
To our knowledge, there is no data in the reported literature about the effect of oral Shohl’s solution on calcium absorption from the intestine and
© 2015 Acta Medica. All rights reserved.
Acta Medica 2015; 4: 5–7
Erden et al.
additionally no data regarding the action mechaA congenital solitary functioning kidney may be
nism of Shohl solution affected by lactose-galacto- an isolated congenital malformation or it may be asse-free diet. However, in our case, the orally admin- sociated with various chromosomal or non-chroistered citrate may have caused hypocalcemia due to mosomal anomalies such as cardiac, genital, skelethe prevention of calcium absorption from the intes- tal, gastrointestinal, urological, and respiratory abtine. A similar mechanism was discussed in a pre- normalities (6). Both congenital solitary kidney and
viously reported case (4). We thus recommend that galactosemia are very rare and separate entities (5,6).
clinicians should be cautious regarding the possi- To date, no previous case with congenital solitary
bility of hypocalcemia while administering Shohl’s kidney accompanied to galactosemia has been resolution in newborns.
ported in the literature.
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[2] Karet FE. Disorders of water and acid-base homeostasis.
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[3] Uras N, Karadag A, Karabel M, Tatli MM. Is bicarbonate
solution tolerated better than Shohl’s solution in neonatal renal tubular acidosis? Pediatr Nephrol. 2007;22:152-153.
[5] Berry GT, Elsas LJ. Introduction to the Maastricht workshop:
lessons from the past and new directions in galactosemia. J
Inherit Metab Dis. 2011;34:249-255.
[6] Dursun H, Bayazit AK, Büyükçelik M, Soran M, Noyan A,
Anarat A. Associated anomalies in children with congenital
solitary functioning kidney. Pediatr Surg Int. 2005;21:456-459.
[4] Morgan DJ, Ho KM. Profound hypocalcaemia in a patient being anticoagulated with citrate for continuous renal replacement therapy. Anaesthesia. 2009;64:1363-1366.
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